NextStep:Study to Evaluate Safety,Efficacy & Tolerability of Rivastigmine Patch in Mild to Moderate Alzheimer's Patients. (ENA1stepswitch)

A 24-week, Open-label, Multicenter Study to Evaluate the Efficacy, Safety and Tolerability of Rivastigmine Patch With 1-step Titration in Patients With Mild to Moderate Alzheimer's Disease (MMSE 10 - 23) Switched Directly From Holinesterase Inhibitors (Donepezil, Galantamine)

To evaluate the efficacy of rivastigmine patch with 1-step titration on cognitive function measured as change from baseline to week 24 in the total score of Mini-Mental State Examination (MMSE) in mild to moderate Alzheimer's disease (AD) patients who failed to benefit from other cholinesterase inhibitors (ChEIs).

Study Overview

• Status: Completed
• Conditions: Mild to Moderate Alzheimer's Disease
• Intervention / Treatment: Drug: Rivastigmine Patch

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Okayama, Japan, 710-0813
    • Novartis Investigative Site
  • Fukuoka
    • Fukuoka city, Fukuoka, Japan, 814 0180
      • Novartis Investigative Site
    • Fukuoka city, Fukuoka, Japan, 814-0015
      • Novartis Investigative Site
  • Fukushima
    • Aizuwakamatsu, Fukushima, Japan, 965-8585
      • Novartis Investigative Site
  • Ibaraki
    • Tsukuba-city, Ibaraki, Japan, 305-8576
      • Novartis Investigative Site
  • Kagawa
    • Kita-gun, Kagawa, Japan, 761-0793
      • Novartis Investigative Site
  • Kanagawa
    • Sagamihara-city, Kanagawa, Japan, 252-5188
      • Novartis Investigative Site
  • Kochi
    • Kochi-city, Kochi, Japan, 780-0842
      • Novartis Investigative Site
  • Niigata
    • Sanjo-city, Niigata, Japan, 955-0823
      • Novartis Investigative Site
  • Okayama
    • Kurashiki-city, Okayama, Japan, 710-0826
      • Novartis Investigative Site
  • Osaka
    • Osaka-city, Osaka, Japan, 543-8555
      • Novartis Investigative Site
    • Suita city, Osaka, Japan, 565 0871
      • Novartis Investigative Site
  • Saitama
    • Kasukabe-city, Saitama, Japan, 344-0036
      • Novartis Investigative Site
    • Koshigaya-city, Saitama, Japan, 343-0032
      • Novartis Investigative Site
  • Shizuoka
    • Fuji city, Shizuoka, Japan, 416-0955
      • Novartis Investigative Site
  • Tokyo
    • Bunkyo ku, Tokyo, Japan, 113-8431
      • Novartis Investigative Site
    • Hachioji-city, Tokyo, Japan, 193-0944
      • Novartis Investigative Site
    • Shinjuku-ku, Tokyo, Japan, 160-0023
      • Novartis Investigative Site
    • Suginami Ku, Tokyo, Japan, 168-8535
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Outpatient status at baseline.
2. Males, and females not of child-bearing potential (surgically sterile, or one year or more from last menses).
3. A diagnosis of dementia of the Alzheimer's type according to the DSM-IV criteria.
4. A clinical diagnosis of probable AD according to National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.
5. Brain scan (magnetic resonance imaging [MRI], or computed tomography [CT]) were met diagnosis criteria conducted within 3 years prior to baseline.
6. Positron emission tomography (PET) or single photon emission computed tomography (SPECT) was met diagnosis criteria conducted within 3 years prior to baseline visit, as long as in the past a brain scan (MRI or CT) also was met.
7. MMSE score of ≥ 10 and ≤ 23 at screening and baseline.
8. Patients are currently on the oral monotherapy (donepezil, 5 mg), or galantamine (16-24 mg) for 4 weeks prior to baseline visit.
9. Patients who failed to receive enough treatment benefit from the previous treatment can be defined if the patients meet at least one of following conditions at screening and baseline (multiple choices allowed)
10. Patients who declined ≥ 2 points of MMSE despite of treatment of other oral Cholinesterase (ChE) inhibitors within initial 3-month and continued to show insufficient treatment effect until at baseline.
11. During 6 months prior to screening visit, patients who declined ≥2 points of MMSE with other oral ChE inhibitors and continued to show insufficient treatment effect until at baseline.
12. Patients who show marked worsening of BPSD, or ADL (can be defined by 1 state progression of FAST) judged by a physician despite of treatment of other oral ChE inhibitors in initial 3-month or last 6-month with other oral ChE inhibitors
13. Patients having difficulties being treated orally with ChEIs (donepezil or galantamine) by physician's judgement.
14. Poor compliance or adverse event except GI symptoms
15. Patients with swallowing difficulties.

Exclusion Criteria:

1. Any medical or neurological condition other than AD that could explain the patient's dementia (e.g., abnormal thyroid function tests, vitamin B12 or folate deficiency, posttraumatic conditions, syphilis, head injury, Huntington's disease, Parkinson's disease, subdural hematoma, normal pressure hydrocephalus, brain tumor) at baseline
2. Any other DSM-IV Axis 1 diagnosis that may interfere with the evaluation of the patient's response to study medication, including other primary neurodegenerative dementia, schizophrenia, or bipolar disorder
3. An advanced, severe, progressive, or unstable disease of any type that may interfere with efficacy and safety assessments or put the patient at special risk
4. Current diagnosis of an active skin lesion/disorder
5. Patients with a history of hypersensitivity to any ingredients of rivastigmine or carbamate derivatives
6. Each patient will be required to have a primary caregiver willing to accept responsibility for supervising treatment, assessing the patient's condition throughout the study, and for providing input into efficacy assessments.

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Rivastigmine Patch; Alzheimer's disease patient who is applicable to 1 step titration method (initial loading dose is a rivastigmine patch 9.0 mg/day and will be up-titrated after 4 weeks to reach the maintenance dose of 18 mg/day). Rivastigmine patch is a marketed drug, therefore the dose, dose regimen and titration scheme are in accordance with product label.	Drug: Rivastigmine Patch; Alzheimer's disease patient who is applicable to 1 step titration method (initial loading dose is a rivastigmine patch 9.0 mg/day and will be up-titrated after 4 weeks to reach the maintenance dose of 18 mg/day). Rivastigmine patch is a marketed drug, therefore the dose, dose regimen and titration scheme are in accordance with product label.; Other Names: rivastigmine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MMSE Total Score: Change From Baseline to Week 8 and Week 24 (Full Analysis Set)	Evaluation of the efficacy of rivastigmine patch with 1-step titration on cognitive function measured as change from baseline to week 24 in the total score of MMSE in mild to moderate Alzheimer's disease (AD) patients who failed to benefit from other cholinesterase inhibitors (ChEIs) The MMSE is a screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement from baseline. Abbreviated Scale title: Mini Mental State Evaluation Minimum Score: 0 Maximum score: 30 Higher score indicated better cognitive function	baseline, weeks 8 and 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MMSE Total Score: Change From Baseline to Week 8 and Week 24	Evaluation of the safety, tolerability of rivastigmine patch with 1-step titration for up to 24 weeks. Per Protocol, The MMSE is a brief, practical screening test for cognitive dysfunction. The MMSE consists of 2 parts: language (time orientation, registration and attention) and performance (recall, response to written/verbal commands, writing ability and reproduction of complex polygons), and the total possible score is 30. Lower score indicates more severe impairment. It is the most common and simple cognitive scale for Alzheimer's disease. Unabbreviated Scale : MMSE - Mini Mental State Evaluation: Minimum values - 0 Maximum value - 30 Higher Value means a better outcome Positive change score from baseline indicates improvement in cognitive function	baseline, weeks 8 and 24
Change From Baseline to Week 8 in Mini-Mental State Examination (MMSE) Total Score	Evaluation of the efficacy of rivastigmine patch with 1-step titration measured as the MMSE score at week 8 for patients who had 1-step titration MMSE total score: change from baseline to Week 8 and Week 24 for patients who had 1-step titration Unabbreviated Scale : MMSE - Mini Mental State Evaluation: Minimum values - 0 Maximum value - 30 Higher Value means a better outcome Positive change score from baseline indicates better outcome	baseline and week 8
Change in Neuropsychiatric Inventory - 10 Item (NPI-10) Score From Baseline to Week 8 and Week 24	Evaluation of the efficacy of rivastigmine patch with 1-step titration measured as the Neuropsychiatric Inventory - 10 Item (NPI-10) score at week 8 and week 24. Per protocol, Neuropsychiatric The NPI-10 total score is a sum of the 10 items, where the score for a domain is defined as the product of frequency (range: 1-4) and severity (range: 1-3). Each domain has a maximum score of 12 and all domains are equally weighted for the total score (thus the range for the total score is 0 to 120). A higher score indicates more severe impairment. Neuropsychiatry Inventory - 10 Minimum Score = 0 Maximum Score = 120 Higher Score indicates worse outcome	baseline, week 8, week 24
Change in QOL-AD Score From Baseline to Week 24	Evaluation of the efficacy of rivastigmine patch with 1-step titration measured as QOL-AD score at week 24. Unabbreviated Scale Name: Quality of Life - Alzheimer's Disease Minimum Score = 13 Maximum Score = 52 Higher value indicates a better outcome QOL-AD is a 13-item questionnaire to assess the quality of life of Alzheimer's patients from the perspectives of patients and their caregivers. It covers several aspects, for example, the perception of health status, mood, functional capacity, personal relationships and leisure, financial situation, and life as a whole. Each item is quantified using a Likert scale with score one classified as poor, and score four as excellent where total scores range from 13 to 52. A lower score indicates more severe impairment.	baseline and week 24
Change in J-CGIC Score From Baseline and at Week 24	Evaluation of the efficacy of rivastigmine patch with 1-step titration measured as the The Japanese-Clinical Global Impression of Change (J-CGIC) score at baseline and week 24 J-CGIC is a 7-grade investigator's impression scale: 1. Markedly improved, 2. Improved, 3. Slightly improved, 4. No change, 5. Slightly aggravated, 6. Aggravated, 7. Markedly aggravated At week 24, 103 patients had available data Total score is in the 0 to 56 range. Higher score means more severe impairment. Unabbreviated scale title: Japanese -Cinical Global Impression of Change Minimum Score - 1 Maximum Score - 7	baseline and week 24
Change in as Modified Crichton Scale Score From Baseline to Week 4, 8, 16 and 24	Evaluation of the efficacy of rivastigmine patch with 1-step titration measured as Modified Crichton Scale score week 4, week 8, week 16, and week 24. Modified Crichton Scale that assess basic activation of daily living, communication functions, and quality of life The following 7 items will be evaluated by caregiver. Total score is in the 0 to 56 range. Higher score means more severe impairment. Unabbreviated Scale Title: Modified Crichton scale Minimum score = 0 Maximum Score = 56 Higher score indicates worse outcome	baseline, weeks 4, 8, 16, 24
Formulation Usability Questionnaire Form Score up to Week 24	Evaluation of the formulation usability of rivastigmine patch for up to 24 weeks as measured by the formulation usability questionnaire answered by caregiver. The Formulation usability preference questionnaire had been used to compare the previous oral AD drugs versus the patch The caregiver selects one of the following answers (1. Very easy to use, 2. Easy to use, 3. No change, 4. Not easy to use, 5. Not easy to use at all, 6. Unknown). This questionnaire data is used to assess if the usability of rivastigmine patch was preferred by the majority (> 50%) of AD patient caregivers or not. Unabbreviated Questionnaire title: Formulation Usability questionnaire Minimum Score = 1 Maximum Score = 6 A higher score indicates its not easy to use and worse outcome.	Up to week 24

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2016
• Primary Completion (Actual): May 7, 2018
• Study Completion (Actual): May 7, 2018

Study Registration Dates

• First Submitted: February 26, 2016
• First Submitted That Met QC Criteria: March 8, 2016
• First Posted (Estimate): March 9, 2016

Study Record Updates

• Last Update Posted (Actual): September 12, 2019
• Last Update Submitted That Met QC Criteria: August 5, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Alzheimer's disease
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Neuroprotective Agents; Protective Agents; Cholinesterase Inhibitors; Rivastigmine
• Other Study ID Numbers: CENA713DJP02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

IPD Plan Description

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No